Overactive bladder is defined as a disease name which causes urinary urgency frequently. Although prostatic hyperplasia may be exemplified as one of the causes for overactive bladder, there are many cases where the cause is ambiguous, which are called idiopathic overactive bladder. Further, although overactive bladder is sometimes accompanied by pollakiuria and urinary incontinence, it is not always limited to the disease accompanied by pollakiuria and urinary incontinence. That is, in the case of mild overactive bladder, a patient is sensitive to the sense of wishing to urinate and frequently has a sense of wishing to urinate but, actually, can hold their urine for a certain period of time. However, even in the case of mild overactive bladder, there is a strong demand for improvement in view of patient QOL (Quality of Life).
On the other hand, severe overactive bladder is sometimes accompanied by pollakiuria and urinary incontinence. Pollakiuria is a state where number of times of urination is more than normal and is usually twice or more at night and eight times or more during 24 hours. Urinary incontinence is defined as a state where there is a problem socially or hygienically due to an involuntary leakage of urine, and is classified into abdominal pressure urinary incontinence that takes place when abdominal pressure is applied such as during coughing or sneezing, urge urinary incontinence in which need of urinate takes place suddenly, with urine leakage before a patient reaches a toilet, mixed-type urinary incontinence of abdominal pressure urinary incontinence with urge urinary incontinence, and the like.
Anticholinergic agents are mainly used for treating symptoms accompanying overactive bladder, but there are some cases where expression of side effects accompanying the anticholinergic actions, such as dry mouth, constipation, blurred vision, or the like, is exhibited. Therefore, it cannot be stated that satisfactory therapeutic results are always achieved. Further, a β3 adrenergic receptor agonist is under a clinical test as a therapeutic agent for overactive bladder at present, but in view of expression of its effects or side effects as a pharmaceutical product, there are still many unclear factors.
Under these circumstances, there is a document which discloses treatment of bladder dysfunction by a pharmaceutical composition containing an antimuscarinic agent and a β3 adrenergic receptor agonist (Patent Document 1).
This document cites a large number of compounds, regarding each of an antimuscarinic agent and a β3 adrenergic receptor agonist to be combined, but has no specific description of combination of (R)-2-(2-aminothiazol-4-yl)-4′-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl}acetanilide or a pharmaceutically acceptable salt thereof and (3R)-quinuclidin-3-yl (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate or a pharmaceutically acceptable salt thereof according to the present invention.
There is a disclosure that (R)-2-(2-aminothiazol-4-yl)-4′-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl}acetanilide has a β3 adrenergic receptor agonistic action and is useful as a therapeutic agent for overactive bladder when used as a single agent (Patent Document 2). In addition, the chemical structure of this compound is as follows and is known as YM178.

There is a disclosure that (3R)-quinuclidin-3-yl (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate has muscarinic M3 receptor antagonistic activities and is useful as a therapeutic agent for unstable bladder when used as a single agent (Patent Document 3). Further, the “unstable bladder” as used in Patent Document 3 has the same meaning as “overactive bladder”. In addition, the chemical structure of this compound is as follows and is also known as solifenacin or YM905.

[Patent Document 1] Pamphlet of International Publication WO 2004/047838
[Patent Document 2] Pamphlet of International Publication WO 2004/041276
[Patent Document 3] Pamphlet of International Publication WO 96/20194